Phenethylamine (PEA) is an amphetamine-like substance which is normally found in the brain. In pilot experiments, we have found that the motor stimulation and unusual stereotyped behavior produced in mice by PEA is intensified during long-term treatment with PEA and that this effect is antagonized by haloperidol. These results suggest that PEA-dependent mechanisms may contribute to schizophrenia and/or the anti-schizophrenic activity of neuroleptic drugs. We propose to investigate the apparent sensitization to PEA which occurs during long-term drug treatment by examining possible changes in PEA metabolism (by MAO), disposition, endogenous content of PEA or PEA induced effects in brain dopamine turnover as a possible contributory factor to the pathophysiology of schizophrenia.